Methotrexate esters of poly(ethylene oxide)-block-poly(2-hydroxyethyl-L-aspartamide).: Part I:: Effects of the level of methotrexate conjugation on the stability of micelles and on drug release
Methotrexate esters of poly(ethylene oxide)-block-poly(2-hydroxyethyl-L-aspartamide).: Part I:: Effects of the level of methotrexate conjugation on the stability of micelles and on drug release
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DOI：
10.1023/a:1007529218802
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发表时间：
2000-05-01
影响因子：
3.7
通讯作者：
Kwon, GS
中科院分区：
文献类型：
--
作者：
Li, Y;Kwon, GS
目的.研究了甲氨蝶呤/甲氨蝶呤（MTX）聚环氧乙烷（PEO）嵌段-聚（2-羟乙基-L-二甲酰胺）酯（MTX）胶束-赋形嵌段共聚物药物偶联物（MTX）的疏水性对胶束稳定性和药物释放的影响。合成了具有三种MTX缀合水平的PEO-b-PHEA的MTX酯。通过动态光散射（DLS）测量胶束的尺寸分布。通过光散射研究确定临界胶束浓度（CMC）。采用体积排阻高效液相色谱法（SEC-HPLC）研究了MTX在pH 7.4时的释放及单聚体与胶束之间的平衡。制备了MTX取代度为7.4%、22%和54%的PEO-b-PHEA的MTX酯。基于DLS，缀合物形成胶束。胶束的稳定性与MTX偶联水平相关。含有54% MTX的缀合物具有比含有22% MTX（0.081 mg/mL）或7.4% MTX（0.14 mg/mL）的缀合物更低的CMC（0.019 mg/mL）。54%MTX偶联物的胶束解离明显慢于22%和7.4%MTX偶联物。MTX：从胶束中释放的较慢也观察到具有较高MTX附着的缀合物。PEO-b-PHEA的MTX酯可以通过改变MTX取代的程度来进行结构调节，这反过来改变了缀合物的疏水性，从而改变胶束稳定性并控制药物释放。
Purpose. To study the effects of hydrophobicity of the micelle-funning block copolymeric drug conjugate, methotrexate /MTX) esters of poly(ethylene oxide)-block-poly(2-hydroxyethyl-L-aspartamide) (MTX esters of PEO-b-PHEA), on the stability of micelles and on drug release.Methods. MTX esters of PEO-b-PHEA with three levels of MTX conjugation were synthesized. Size distribution of the micelles was measured by dynamic light scattering (DLS). The critical micelle concentration (CMC) was determined by a light scattering study. Size exclusion high performance liquid chromatography (SEC-HPLC) was used to study the equilibrium between unimers and micelles, and release of MTX at pH 7.4.Results. MTX esters of PEO-b-PHEA with MTX substitution of 7.4%, 22%, and 54% were prepared. The conjugates formed micelles based on DLS. The stability of the micelles correlated with the level of MTX conjugation. The conjugate with 54% MTX had a lower CMC (0.019 mg/mL) than the conjugates with 22% MTX (0.081 mg/mL) or 7.4% MTX (0.14 mg/mL). Micelle dissociation was significantly slower for the conjugate with 54% MTX than that with 22% and 7.4% MTX. Slower release of MTX: from the micelles was also observed for the conjugate with the higher MTX attachment.Conclusions. MTX esters of PEO-b-PHEA can be structurally modulated by varying the degree of MTX substitution, which in turn changes the hydrophobicity of the conjugate, thereby modifying micelle stability and controlling drug release.